| 1. |
- Joshi, Peter K, et al.
(författare)
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Directional dominance on stature and cognition in diverse human populations
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
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Tidskriftsartikel (refereegranskat)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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| 2. |
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| 3. |
- Botvinik-Nezer, Rotem, et al.
(författare)
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Variability in the analysis of a single neuroimaging dataset by many teams
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
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Tidskriftsartikel (refereegranskat)abstract
- Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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| 4. |
- Frazier-Wood, Alexis C., et al.
(författare)
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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
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Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
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Tidskriftsartikel (refereegranskat)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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| 5. |
- Johannesson, Magnus, et al.
(författare)
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Hypothetical versus real willingness to pay in the health care sector: results from a field experiment
- 2001
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Ingår i: Journal of health economics. - : Elsevier B.V. - 1879-1646 .- 0167-6296. ; 20:3, s. 441-457
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a field experiment comparing hypothetical and real purchase decisions for a pharmacist provided asthma management program among 172 subjects with asthma. Subjects received either a dichotomous choice contingent valuation question or were given the opportunity to actually enroll in the program. Three different prices were used: US$ 15, 40, and 80. In the hypothetical group, 38% of subjects said that they would purchase the good at the stated price, but only 12% of subjects in the real group purchased the good ( p=0.000). We cannot, however, reject the null hypothesis that “definitely sure” hypothetical yes responses, as identified in a follow-up question, correspond to real yes responses. We conclude that the dichotomous choice contingent valuation method overestimates willingness to pay, but that it may be possible to correct for this overestimation by sorting out “definitely sure” yes responses.
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| 6. |
- Nettelbladt, Ulrika, et al.
(författare)
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A Multidisciplinary Assessment of Children with Severe Language Disorder
- 1989
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Ingår i: Clinical Linguistics & Phonetics. - : Informa UK Limited. - 1464-5076 .- 0269-9206. ; 3:4, s. 313-346
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Tidskriftsartikel (refereegranskat)abstract
- This study presents results from a multidisciplinary assessment of ten Swedish children with severe language disorder, aged 4;4-10;0. The children underwent an extensive medical examination. They were also tested by a clinical child psychologist. A thorough neurolinguistic examination was done as well as detailed linguistic analyses of the children's speech production. The results of our study revealed few links between medical findings and findings in other areas. One exception regards the outcome of the neurolinguistic, the linguistic and audiological assessments, where a possible link between auditory comprehension deficits and certain phonological and syntactic features are discussed. The authors suggest that detailed case studies are the only way at present to elucidate crucial individual differences in language disordered children, in particular in children with severe language disorders. In the future we hope that such studies may increase the knowledge on which typologies of such children can be based and to help us develop more adequate and effective means of intervention.
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| 7. |
- Smith, Jennifer A, et al.
(författare)
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Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
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Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
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| 8. |
- Zillich, Alan J, et al.
(författare)
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Assessment of the relationship between measures of disease severity, quality of life, and willingness to pay in asthma
- 2002
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Ingår i: PharmacoEconomics. - : Adis International. - 1179-2027 .- 1170-7690. ; 20:4, s. 257-265
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The primary objective was to evaluate the relationship between willingness-to-pay (WTP), quality-of-life (QOL), and disease-severity measures in patients with asthma. The hypothesis studied was that patients with asthma with more severe disease are willing to pay more for a hypothetical cure of asthma than those with less severe disease. Design setting/Patients and participants: One hundred patients with asthma were recruited from community pharmacies in Kentucky for 30-minute face-to-face interviews. Interventions: Spirometry assessed objective disease severity in terms of pulmonary function, while a multiple choice question measured subjective disease severity. The Medical Outcomes Study 36-item Short Form (SF-36) health survey and Asthma Technology of Patient Experience (Asthma TYPE) measured quality of life. WTP was obtained via a dichotomous choice contingent valuation question. Results: In this exploratory evaluation, WTP was significantly related to both objective disease severity (p = 0.02) and subjectively assessed disease severity (p = 0.01). For objective disease severity the mean monthly WTP was $US90 for mild asthma, $US131 for moderate asthma and $US331 for severe asthma and for subjective disease severity the mean monthly WTP was $US48 for mild asthma, $US166 for moderate asthma and $US241 for severe asthma. Conclusions: The results suggest that the WTP for a cure from asthma is related to both objective and subjective disease severity. These findings contribute to the case for construct validity of the dichotomous choice contingent valuation method in the healthcare sector.
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